Asian Pac. J. Health Sci.

, 2014; 1(3):200-206 ISSN: 2349-0659

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ROLE OF PHOTODYNAMIC THERAPY IN PERIODONTITIS

SAXENA S1*, BHATIA G2, GARG B3, RAJWAR YC4

1
Department of Periodontology, Institute of Dental Studies & Technologies, Modinagar, U.P, India
2
Department of Periodontology, Eklavya Dental College, Kotputli, Jaipur, Rajasthan, India
3
Department of Oral & Maxillofacial Surgey, Eklavya Dental College, Kotputli, Jaipur, Rajasthan, India
4
Department of Oral Pathology and Microbiology, Eklavya Dental College, Kotputli, Jaipur, Rajasthan, India

ABSTRACT

The etiology of periodontitis is multifactorial and the anatomical complexity of tooth roots serves as niches for
bacterial deposits, making eradication of periodontopathogens more difficult both mechanically and chemically.
Also, the fact that conventional treatment such as scaling and root planing (SRP) does not completely eliminate
periodontal pathogens, led to the use of various adjuvant treatments modalities. A novel noninvasive photochemical
approach for infection control, namely photodynamic therapy, has received much attention in the treatment of oral
diseases. Three nontoxic ingredients namely visible harmless light, a photosensitizer and oxygen are involved in this
therapy. It is based on the principle that a photosensitizer binds to the target cells which when activated by light of a
suitable wavelength results in the production of singlet oxygen and other very reactive agents that are extremely
toxic to certain cells and bacteria. This article highlights the role of photodyanamic therapy in periodontitis.

Keywords: Antimicrobial, periodontitis, photodynamic therapy, photosensitizer.

Introduction

The application of light energy (phototherapy) has been
considered as a novel treatment approach in periodontics.
Dental lasers have been used as an effective means of
decontamination of periodontal pockets over a period of
20 years[1]. Lasers possess high bactericidal properties
and have demonstrated effective killing of oral
pathogenic bacteria associated with periodontitis and
peri-implantitis[2]. Most high-level lasers exhibit
bactericidal effects by thermal denaturation or direct
ablation or destruction of bacterial cells and have been
applied in nonsurgical or surgical periodontal and peri-
implant therapies.
_______________________________
*Correspondence
Dr. Sameer Saxena
Senior Lecturer,
Department of Periodontology,
Institute of Dental Studies & Technologies, U.P., India
Email: saxena.sameer27@gmail.com
Besides damaging the bacterial cells, the use of high-
level lasers results in irreversible thermal damage to the
surrounding periodontal tissues, excessive ablation or
thermal coagulation, carbonization or necrosis of the
root, the gingival connective tissue, the bone and the
pulp tissues, depending on the type of laser
employed[3].Photodynamic therapy is a new type of
noninvasive phototherapy for bacterial elimination,
which uses low-level laser light and selectively targets
the bacteria without potentially damaging the host
tissues[1].
Historical perspective of photodynamic therapy
The origin of light as a therapy in medicine and surgery
has been traced from antiquity to the modern day.
Phototherapy began in ancient Greece, Egypt and India,
but disappeared for many centuries, only being
rediscovered by the Western civilization at the beginning
of the 20th century. The use of contemporary
photodynamic therapy was first reported by the Danish
physician, Niels Finsen (1901). He successfully
demonstrated photodynamic therapy by employing heat
– filtered light from a carbon – arc lamp (The Finsen

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Lamp) in the treatment of a tubercular condition of the
skin known as Lupus Vulgaris. Niels Finsen won a nobel
prize for his work on phototherapy in 1903. [1,4]
The concept of cell death induced by the interaction of
light and chemicals was first
st reported by Osar Raab[5]
Raa a Components of PDT
medical student working with Professor Herman Von
Tappeiner in Munich. During the course of his study on
the effects of acridine on paramecia cultures, he
discovered that the combination of acridine red and light
had a lethal effect on infusoria, a species of paramecium.
Subsequent work in the laboratory of Von Tappeiner
(1907) coined the term “Photodynamic action” and
showed that oxygen was essential. Much later, Thomas
Dougherty and co-worker[6] at Roswell Park cancer
institute,
te, Buffalo, New York, clinically tested
Photodynamic therapy. In 1978, they published striking
results in which they treated 113 cutaneous or
subcutaneous malignant tumors and observed a total or
partial resolution of 111 tumors. The active
photosensitizerr used in this clinical trial was called
Hematoporphyrin Derivative. It was John Toth, who
renamed it as Photodynamic therapy.
ISSN: 2349-0659
Photodynamic therapy was approved by the Food and
Drug Administration in 1999 to treat pre-cancerous
pre skin
lesions of the face or scalp. PDT has emerged in recent
years as a new non - invasive therapeutic option.
Photodynamic therapy basically involves three non-toxic
non
ingredients: visible harmless light, a nontoxic
photosensitizer and oxygen. (Figure
(Fi 1) It is based on the
principle that a photosensitizer (i.e. a photoactivatable
substance) binds to the target cells and is activated by
light of a suitable wavelength. Following activation of
the photosensitizer through the application of light of a
certain wavelength, singlet oxygen and other very
reactive agents are produced that are extremely toxic to
certain cells and bacteria. The photosensitizer is
generally applied in the targeted area by topical
application, aerosol delivery or interstitial injection.
in The
light that activates the photosensitizer must be of a
specific wavelength with a relatively high intensity[1].
intensity

Light

Photosensitizer Oxygen

Figure 1: Basic components of photodynamic therapy

Light

Sources of light include a range of lasers, helium - neon light between 630 and 700 nm corresponding to a light
lasers (633 nm), gallium - aluminum - arsenide diode penetration depth
epth from 0.5 cm (at 630 nm) to 1.5 cm at
lasers (630-690,
690, 830 or 906 nm) and argon laser (488 (488- (700 nm) which is sufficient for periodontal treatment.[7]
514nm), the wavelength of which range from visible The total light dose, dose rates and the depth of
light to the blue of argon lasers, or fro from the red of destruction vary with each tissue treated and
helium-neon
neon laser to the infra red area of diode lasers. photosensitizer used[8].
Non-laser
laser light sources like light emitting diode (LED)
and light cure units. Photosensitizers are activated by red
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Photosensitizers therapy. After irradiation with light of a specific
wavelength (lasers), the photosensitizer at ground state is
A photosensitizer
zer is a dye substance that is absorbed by activated to a highly energized triplet state. The longer
the microorganism, cell or tissue allowing it to interact lifetime of the triplet state enables the interaction of the
with the light. An optimal photo sensitizer must possess excited photo sensitizer with the surrounding molecules
photo-physical,
physical, chemical and biological characteristics. resulting in the generation of cytotoxic species. There are
The sensitizers used for medical purposes belong to the two different pathways (type I and II) to react with
following basic structure: [7] biomolecules. [1,11]
1. Tricyclic dyes with different meso
meso-atoms E.g.:
Acridine orange, proflavine, riboflavin, Type I reactions involve hydrogen-atom
hydrogen abstraction or
methylene blue, fluorescein and erythrosine. electron-transfer
transfer reactions between the excited state of
2. Tetrapyrroles. E.g.: Porphyrins and derivatives, the photosensitizer and an organic substrate molecule of
chlorophyll, phylloerythrin and the cells, which produces free radicals and radical ions.
phthalocyanines. These free-radical
radical species are highly reactive and
3. Furocoumarins. E.g.: Psoralen and its interact with endogenous molecular oxygen
ox to produce
methoxyderivatives, xanthotoxin and highly reactive oxygen species such as superoxide,
bergaptene. hydroxyl radicals and hydrogen peroxide, which are
harmful to cell membrane integrity and result in
In antimicrobial PDT, photosensitiz
photosensitizers used are toluidine irreparable biological damage [11]. (Figure 2)
blue O and methylene blue. Both have similar chemical
and physicochemical characteristics. The positive charge In the type II reaction, the triplet-state photosensitizer
seems to promote the bindinging of the photosensitizer to reacts with oxygen to produce a highly reactive state of
the gram-negative
negative bacterial membrane and leads to its oxygen, known as singlet oxygen (1O2), which interacts
localized damage,
mage, resulting in an increase in its with a large number of biological substrates due to its
permeability. Methylenelene blue interaction with the high chemical reactivity, inducing oxidative damage and
anionic lipopolysaccharide macromolecule of gram- gram ultimately
timately lethal effects upon the bacterial cell by
negative bacteria results in the generation of methylene damaging the cell membrane and cell wall. Singlet
blue dimers, which participate in the photosensitization oxygen has a short lifetime in biological systems (<0.04
process [9,10] µs) and a very short radius of action (0.02 µm) that
causes limited migration of singlet oxygen from fr its site
Mechanism of action of formation leading to a localized response and making
it ideal for application at localized sites without affecting
The bactericidal effect of photodynamic therapy is distant molecules, cells or organs. The process of
explained by two potential, but different, mechanisms antimicrobial photodynamic therapy is generally
namely the DNA damage and the damage caused to the mediated by a type II reaction,
reac which is accepted as the
cytoplasmic membrane of the bacteria by cytotoxic major pathway in microbial cell damage.[11,12] (Figure 2)
species generatedd by antimicrobial photodynamic

Figure 2: Mechanism of photodynamic antimicrobial reaction at the molecular level[1]

level

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Photodynamic therapy in the treatment of oral
diseases
Applications of photodynamic therapy in dentistry
include photodynamic diagnosis of malignant oral
lesions, treatment of premalignant and malignant oral
lesions and photodynamic antimicrobial chemotherapy
(PACT) of bacterial and fungal infections. The various
uses are as follows: [1, 13]
1. Treatment of different types of oral solid tumors
2. Treatment of psoriasis, actinic keratosis
3. Treatment of inflammatory diseases like
rheumatoid arthritis
4. Age related macular degeneration
5. Superficial precancerous oral lesions, such as
oral leukoplakia, oral erythroleukoplakia, oral
verrucous hyperplasia and lichen planus.
6. Treatment of Bacterial, fungal and viral
infections of the oral cavity.
7. Treatment and prevention of dental caries.
8. As an adjunct to conventional endodontic
disinfection treatment to destroy the bacteria
that remain even after irrigation with sodium
hypochlorite
9. Effective in the destruction of Candida albicans,
which is responsible for oropharyngeal
candidiasis
10. Elimination of bacteria in supragingival and
subgingival plaque.
11. As an adjunctive for bacterial elimination in the
treatment of periimplantitis
Photodynamic therapy and Periodontitis
Biofilm in oral cavity causes two of the most common
diseases, dental caries and periodontal diseases. An
effective approach of periodontal therapy is to change
the local environment to suppress the growth of
periodontal pathogens. Using antimicrobial agents to
treat periodontitis without disruption of the biofilm
ultimately results in treatment failures. It is difficult to
maintain therapeutic concentrations at the target sites and
target organisms can develop resistance to drugs. This
resistance is minimized by using PDT. Polysaccharides
present in extracellular matrix of oral biofilm are highly
sensitive to singlet oxygen and susceptible to
photodamage. Breaking the biofilm may inhibit plasmid
exchange involved in transfer of antibiotic resistance and
disrupt colonization[14,15] Photodynamic antimicrobial
chemotherapy could be an ideal complement to
conventional scaling and root planing. However,
bacterial eradication from dental plaque-derived biofilms
is still at a lower level compared to the planktonic
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condition. In the study conducted by Fontana et al [16]
photodynamic therapy eliminated approximately 63% of
bacteria in the planktonic phase as compared to 32% of
bacteria in biofilms, derived from the same plaque
samples.
During inflammation there is venous stagnation and
reduced oxygen consumption by tissues. This decrease in
oxygen level and change in pH enhances the growth of
anaerobic species. PDT improves tissue blood flow in
the microcirculatory system and reduces venous
congestion in gingival tissues. Furthermore, PDT
increases oxygenation of gingival tissues by 21–47 per
cent which in turn decreases the time and speed of
oxygen delivery and utilization, thus normalizing oxygen
metabolism in periodontal tissues [17]
The pathogenesis of periodontal diseases is explained on
the basis of the virulence factors possessed by the
periodontopathogens that cause activation of
macrophages, production of interleukin-1, release of
prostaglandin E2, which are potent stimulators of bone
resorption. Endotoxin on root surface inhibits fibre
reattachment on cementum. PDT causes the inactivation
of the various virulence factors secreted by micro-
organisms. [18]
Upon interpretation of the data from various controlled
clinical studies, the adjunctive use of PDT to scaling and
root planning in the treatment of patients with chronic
periodontitis, aggressive periodontitis and peri-
implantitis, resulted in greater clinical attachment level
gains, reduction in bleeding on probing and probing
pocket depths. Azarpazhooh et al[19] conducted a
systemic review and concluded that photodynamic
therapy as an independent therapy or as an adjunct to
SRP was not superior to control treatment than SRP. A
meta-analysis was performed by Sgolastra et al[20]
which suggested that the use of aPDT as an adjunct to
conventional treatment provides short-term benefits in
terms of CAL gain and pocket depth reduction (at 3
months after treatment ) thereby confirming the safety of
PDT.
PDT has advantage such as reducing the treatment time
(<60seconds), no need for anesthesia, destruction of
bacteria, inactivation of endotoxins, non-invasive local
therapy, reduced risk of bacteraemia after periodontal
debridement and no damage to the adjacent host
tissues[14,21].
Current status and future perspectives
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In the dental field, photodynamic therapy is approv
approved for treatment kits of methylene blue. A kit that includes
the palliative treatment of patients with advanced head phenothiazine chloride for clinical photodynamic therapy
and neck cancer and in the treatment of various oral is now available in Austria, Germany,
Germa Switzerland and
activated disinfection system, PADTM
lesions. Photo-activated the UK (Helbo; Photodynamic Systems GmbH & Co.
(Denfotex Light Systems Ltd, Inverkeithing, UK), is KG, Grieskirchen, Austria). Similar kits that include
used for the disinfection of root canals.
ca The PADTM toluidine blue O are also available from other companies,
consists of toluidine blue O solution and a 100 mW including Denfotex Ltd., Dexcel Pharma Technologies
diode laser that emits light at 635 nm. Toluidine blue O Ltd., SciCan Medtech AG and
a Cumdente
(12.7 mg ⁄l)
l) is applied in the root canals for 60 seconds GmbH[22].(Figure 3,4)
followed by exposure to light via a fiberoptic for 2 min.
Photodynamic therapy
rapy rapidly eliminates The application of these kits is very simple and
microorganisms unlike the conventional therapy[22].
therapy convenient. Methylene blue is applied directly in the
Recently, in Canada, the product called Periowave dental pockets for 60 seconds followed by exposure to
(http://www.periowave.com) was commercialized by red light via a fiberoptic probe for 60 seconds per pocket
Ondine Biopharma Corporation or perr tooth (10s per site, six sites in total). In the
(http://www.ondinebiopharma.com) for the treatment of o majority of the studies, photodynamic therapy was used
periodontitis. The Periowave product consists of a laser as an adjunct to scaling and root planing. (Figure 5)
system with a custom-designed
designed handpiece and patient

Figure 3: Periowave Figure 4: Helbo® T-Controller

Controller
(From: www.bredent-medical.com
medical.com)

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Figure 5: Steps of application of photodynamic therapy in the treatment of periodontitis.

(A) Periodontally diseased site before treatment. (B) Mechanical debridement using hand curettes. (C)Application of
the photosensitizer via syringe at the diseased site that contains residual bacteria. (D) Photosensitization is performed
using an intensive light by a special tip applied in the pocket. Singlet oxygen and other very reactive agents that are
toxic to bacteria are produced, resulting in photochemical disinfection of the periodontal pocket. (E) Improved wound
healing in the treated site.[1]

Conclusion

Antimicrobial photodynamic therapy is likely to be an at-
tractive option as a non-invasive treatment approach in
the field of periodontology, with confirmed clinical
safety. Antimicrobial photodynamic treatment has been
reported to be effective as an adjunct to conventional
therapy to destroy bacteria in sites where there is limited
access for mechanical instrumentation as a result of the
anatomical complexity of the roots. Also, further
randomized long-term clinical studies and meta-analyses
are necessary to demonstrate the beneficial effects of
antimicrobial photochemical therapy and their real
advantages in comparison with conventional methods.
Only then antimicrobial photodynamic therapy will hold
promise as a substitute for currently available
chemotherapy in the treatment of periodontal and peri-
implant diseases.
References
1. Takasaki AS, Aoki AI, Mizutani KJ, Schwarz F,
Sculean A, Wang CY et al. Application of
Antimicrobial Photodynamic Therapy in
Periodontal and Peri-Implant Diseases.
Periodontol 2000 .2009; 51:109–140.
2. Ando Y, Aoki A, Watanabe H, Ishikawa I.
Bactericidal effect of erbium YAG laser on
periodontopathic bacteria. Lasers Surg Med.
1996: 19: 190–200.
____________________________________________________________________________________________________________________________________________
Saxena et al ASIAN PACIFIC JOURNAL OF HEALTH SCIENCES, 2014; 1(3):200-206
www.apjhs.com
3. Aoki A, Sasaki KM, Watanabe H, Ishikawa I.
Lasers in nonsurgical periodontal therapy.
Periodontol 2000.2004:36: 59–97.
4. Rajesh S, Koshi E, Philip K, Mohan A.
Antimicrobial photodynamic therapy: An
overview. J Indian Soc Periodontol. 2011;
15:323–7.
5. Raab O. The effect of fluorescent agents on
infusoria. Z Biol. 1900; 39:524–526.
6. Dougherty TJ, Kaufman JE, Goldfarb A,
Weishaupt KR, Boyle D, Mittleman A.
Photoradiation therapy for the treatment of
malignant tumors. Cancer Res 1978; 38:2628–35.
7. Nagpal S, Dodwad V, Vaish S. Photodynamic
therapy:-A novel approach towards dentistry.
Journal of Pharmaceutical and Biomedical
Sciences.21 ;( 14):1-4.
8. Hopper C, Speight PM, Bown SG.Photodynamic
therapy, an effective, but non selective treatment
for cancers in the oral cavity. Int J Cancer. 1997;
71:937-42.
9. Chan Y, Lai CH. Bactericidal effects of different
laser wavelengths on periodontopathic germs in
photodynamic therapy. Laser Med Sci 2003;
18:51-5.
10. Usacheva M.N., Teichert M.C., Biel M.A.: The
interaction of lipopolysaccharides with
phenothiazine dyes. Lasers Surg. Med 2003;
33:311-19.
205
Asian Pac. J. Health Sci., 2014; 1(3):200-206
____________________________________________________________________________________________________________________________________________
11. Foote C.S. Definition of type I and type II
photosensitized oxidation. Photochem Photobiol
1991; 54:659.
12. Ewa Mielczarek-Badora1, Małgorzata Szulc2.
Photodynamic Therapy and its Role in
Periodontitis Treatment. Postepy Hig Med Dosw
(online), 2013; 67:1058-65.
13. Rajvir M, Anish M,Suresh DK. Photodynamic
therapy: A strategic review. Ind J Dent Resarch
2010; 21(2):285-91.
14. Raghavendra M, Koregol A, Bhola S.
Photodynamic therapy: a targeted therapy in
periodontics. Australian Dental Journal 2009;
54(1):S102–S109.
15. Wood S, Nattress B, Kirkham J. An in vitro study
of use of photodynamic therapy for the treatment
of natural oral plaque biofilms formed in vivo. J
Photochem Photobiol B 1999; 50:1–70.
16. Fontana C.R, Abernethy AD, Som S, Ruggiero K,
Doucette S. Marcantonio RC et al. The
antibacterial effect of photodynamic therapy in
dental plaque-derived biofilms. J Periodont Res
2009; 44: 751-59.
Source of Support: NIL
Conflict of Interest: None
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Saxena et al ASIAN PACIFIC JOURNAL OF HEALTH SCIENCES, 2014; 1(3):200-206
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ISSN: 2349-0659
17. Tanaka M, Hanioka T, Takaya K, Shizukuishi S.
Association of oxygen tension in human
periodontal pockets with gingival inflammation. J
Periodontol 1998; 10:1127–1130.
18. Komerik N, Wilson M, Poole S. The effects of
photodynamic on two virulence factors of Gram
negative bacteria. Photochem Photobiol 2000;
72:676–680.
19. Azarpazhooh A, Shah PS, Tenenbaum HC,
Golberg MB. The effect of photodynamic therapy
for periodontitis: a systematic review and meta-
analysis. J. Periodontol 2010; 81: 4-14.
20. Sgolastra F, Petrucci A, Gatto R, Marzo G,
Monaco A. Photodynamic therapy in the
treatment of chronic periodontitis: a systematic
review and meta-analysis. Lasers Med Sci 2013;
28:669-82.
21. Malik R, Manocha A, Suresh DK. Photodynamic
therapy- A strategic review. Indian J Dent Res
2010; 21:285-91.
22. Soukos NS, Goodson JM. Photodynamic therapy
in the control of oral biofilms. Periodontol 2000.
2011; 55:143–166.
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